TOP 10 reasons dogs/cats visit vets VPI 2012

Transcription

1 + Therapeutic Approach to Canine Allergic Skin Diseases in Veterinary Dermatology Anthony Yu, DVM, MS, Dipl. ACVD Guelph Veterinary Specialty Hospital TOP 10 reasons dogs/cats visit vets VPI 2012 Top 10 Canine Claims Top 10 Feline Claims 1. Ear infections 1. Lower urinary tract diseases 2. Skin allergies 2. Stomach upsets/gastritis 3. Pyoderma (hot spots) 3. Renal failure 4. Stomach upsets 4. IBD/diarrhea 5. IBD/diarrhea 5. Skin allergies 6. Bladder diseases 6. Diabetes 7. Eye infections 7. Colitis/Constipation 8. Arthritis 8. Ear infections 9. Hypothyroidism 9. Upper respiratory virus 10. Sprains 10. Hyperthyroidism How would I treat this moderately Atopic dog? 1

2 That was then.. J Am Vet Med Assoc Jul 15;241(2): Current understanding of the pathophysiologic mechanisms of canine atopic dermatitis. Marsella R, Sousa CA, Gonzales AJ, Fadok VA. This is NOW! J Am Vet Med Assoc Jul 15;241(2): Current understanding of the pathophysiologic mechanisms of canine atopic dermatitis. Marsella R, Sousa CA, Gonzales AJ, Fadok VA. The neurogenic role of itch Sonja Ständer, Itch in Atopic Dermatitis Pathophysiology and Treatment Acta Dermatovenerol Croat 2010;18(4): Histamine 1 and 4 receptor H1 = Erythema, wheal and flare H4 = up-regulation of pruritogenic IL31 Neuropeptides Sub-P, Vasoactive intestinal peptide, somatostatin, neurotensin IL31 by Staphylococcal superag, Malassezia zymosan Neurotrophin-4 by PGE2 Eosinophil-derived neurotoxin 2

3 + TH-1: TH-2 Cell Paradigm T Helper-1 Local IDS IFN-γ, IL2 2ry Yeast Bacteria Fungal Parasitic Viral T-reg, IL-10 TARC Eotaxin T Helper-2 Humoral IDS IL4, 5, 13, 31 SP, NT4, EDN è Allergies Pech Merle Dordogne River France + Multi-Modal Therapy Antineuronal therapy 3

4 + Repairing the Epidermal Barrier In the hands of the primary veterinarian n Minimize TEWL and allergen penetration n Topical replacement therapy n Ceramides, free fatty acids (Allerderm SpotOn, Virbac) n Phytosphingosine (Douxo, Sogeval) n Omega 3 and 6 fatty acids (Dermoscent, LDCA/Aventix) + Repairing the Epidermal Barrier In the hands of the primary veterinarian n Dietary replacement therapy n Pantothenic acid, n Inositol n Nicotinamide n Choline n Histidine n Skin Support (Royal Canin) n Omega 3/6 fatty acids n various diets & supplements + Cetirizine: my new favorite antihistamine n H 1 -antihistamines act as inverse agonists that bind and stabilize the inactive form of H 1 -receptors n Classification based on: Chemical Grouping Ethanolamines Alkylamines Piperazines Piperidines Phenothiazines Ethylenediamines Generations 1 st generation = sedating 2 nd generation = non-sedating 3 rd generation (derivatives of 2 nd gen and this nomenclature should be reserved for next true class of antihistamines to be developed) 4

5 + Piperazines 1 st generation n Antiemetic properties n hydroxyzine (Atarax, Vistaril ) Hydroxyzine 2 nd generation n Active metabolite of hydroxyzine n Min crossing of BBB n Canada: Reactine, USA: Zyrtec n mg/kg Q12-24hrs n 1 mg/ml, 5mg, 10mg n ~ $ /Tx/10kg pet n Combine with amitriptyline/doxepin n Combine with t-butyl carbamate derivatives of aminopyridine (H4 antagonist) + Immunotherapy n Indications: n Cannot avoid allergens n Signs present > 4-6 months n Antipruriticsè side effects or incomplete control n Benefits n Not as treatment intensive n Minimal side effects n Weight independent dosing n Eventuate of a cure Client Education: Injections administer sub-q Sublingual option twice daily Response may take up to 1 year Treatment usually lifelong + ASIT based on IDT or SAT n My personal response rates: n ASIT based on SAT = 40-60% n ASIT based on IDT = 60-80% n Combined = 75-90%+ n Sublingual immunotherapy (SLIT) n Heska, Bio-Medical n BID oral drops n Follow-up and client education paramount to success 5

6 + What drug(s) do I use? n First time pruritic patient n EFAs, AH, Atopica n Acute Flare-up of pruritus (<30d) n Steroids (dexamethasone, Vanectyl-P) n Pruritus lasting 4-6 months n Atopica +/- alternating/pulse steroids n Pentoxifylline +/- alternating/pulse steroids n Pruritus lasting greater than 4-6 months n Immunotherapy +/- Atopica, pulse steroids Atopica (cyclosporine) Update n Anti-inflammatory n Anti-neurogenic n Calcineurin inhibition on nerves n Bind capsaicin receptor TRPV1 è burn è cool n How to institute n 5mg/kg/day for days n +/-With steroids to start 7-14d n Multi-modal therapy n Client expectations n Recheck in 4 weeks n 25% Decrease to 5 mg/kg q48h n Recheck in 8 weeks n 50% Decrease to 5 mg/kg q48-72h Westies best Atopica responders Scruffie Hoch 8 weeks Atopica 6

7 + GINGIVAL HYPERPLASIA n Cyclosporin increases intracellular Ca2+ n Collagenase is regulated by Ca2+ influx è Fibroblasts produce an inactive form of collagenase è Increased extracellular matrix Lin et al., 2007 n More often when CSA + KCZ n Gingival resection n REVERSIBLE n Azithromycin toothpaste or orally + Hirsutism n Cyclosporin prolongs the anagen phase of the hair cycle n Cyclosporin inhibits the expression of Protein kinase C è stimulating hair follicle growth and hair fibre production HARMON et al., 1995 TAKAHASHI AND KAMIMURA, Rocky 8 weeks post-atopica Can I give this to my husband? 7

8 Atopica 4 week recheck Continue or decrease to every other day? Next year, start at EOD 1 month prior to allergy season Preventative therapy for atopy n Patients with known seasonal allergies n Treat atopy BEFORE it becomes a forest fire n Start medications at MAINTENANCE dose n Start 1 month PRIOR to start of season n Vanectyl-P 1 tab/10kg every q48-72h n Atopica 5mg/kg q48-72h n PREVENT inflammation n PREVENT secondary infections n PREVENT side effects n Max Pred dose/yr = 30mg X BW in kg + Calcinosis Cutis due to Steroids 8

9 + Iatrogenic effects of steroids ALTERNARIA MUSCLE ATROPHY/CALCINOSIS CUTIS Adult-onset demodicosis iatrogenic steroids = most common cause What about a severe allergic case like Honey Bear? 9

10 + Gray L, et al The effect of ketoconazole on whole blood and skin concentrations of cyclosporine Vet Derm 2012:23 suppl:13 n N=6 research hounds; randomized cross-over study n Daily for 7d w/14d washout; D1,4,7 - Blood 1.4h/24h, Skin 4h/24h n T1 = 5mg/kg Atopica n T2 = 2.5mg/kg CSA n T3 = 2.5mg/kg CSA + 5mg/kg KCZ n T4 = 2.5 mg/kg CSA mg/kg KCZ n Blood: T3 (644ng/ml)>>T4 (417ng/ml), T1 (307ng/ml), T2 (169 ng/ml) n Skin: T3 (1.2 ng/mg)>>t4 (0.7ng/mg), T1 (0.6ng/mg)>T2 (0.26ng/mg) n 5mg/kg CSA = 2.5mg/kg CSA mg/kg KCZ Honey Bear 8-weeks after + Directions for the future n ID gene markers to breed out Atopic Dermatitis n Stimulate the Th1 and Treg arm of immune system n Medical grade endoparasite n Re-Poop-ulate n Bacterial DNA motifs n Target specific mediators of inflammation n Monoclonal antibodies n Anti-IL-5, anti-tnf-α? anti- CCR4? n Janus Kinase inhibitors n Anti-IgE (Xolair - $10-12K/year) n Potentiated ASIT n CpG motifs, lysosomes, cell wall extracts Mueller RS et al. The effect of nematode administration on canine atopic dermatitis Vet Parasit 2011;181(2-4):

11 + Neurogenic Itch n Gabapentin (Neurontin ) n Dec Ca++ influx è inhibit excitatory neurotransmitters n 5-10mg/kg TID n Avoid oral solution (Neurontin ) - contains 300 mg/ml xylitol. n Maropitant citrate (Cerenia ) n neurokinin-1 receptor antagonist è inhibiting Substance P n 1-2 mg/kg once daily for 4 days, then 2-3X weekly. n Combine both therapies in severe steroid non-responsive itch + Janus Kinase Inhibitors Apoquel (Pfizer) Allerquel for Canada? MOA: n inhibiting JAK family of enzymes (JAK1,2,3 or TYK2) n interfering with the JAK-STAT signaling pathway (receptor, JAK, and STAT (Signal Transducer and Activator of Transcription) n Humans: psoriasis, rheumatoid arthritis, neoplasia, polycythemia vera, etc. n Blocks IL-31 (pruritogenic) binding and activation of JAK/STAT. n 0.4mg/kg BID n Vet Derm 2012;23 Suppl:38-39 n Cosgrove S et al. Multicentre clinical trial to evaluate the efficacy and field safety of oclacitinib n=341 dogs, placebo matched study, significant improvement 14d, V/D n Fleck T et al. Comparison of Janus Kinase inhibitor oclacitinib, and prednisolone in canine models of pruritus Oclacitinib >> and faster than prednisolone n Wheeler DW et al. Oclacitinib for the treatment of pruritus and lesions associated with canine flea-allergi dermatitis n-36 FAD sig improvement in VAS 0.4, 0.8mg/kg>>Placebo Victoria BC Butchart Gardens Sunken Garden old lime quarry 11